Structural studies of the glycine decarboxylase complex from pea leaf mitochondria.
The glycine decarboxylase complex consists of four different component enzymes (P-, H-, T- and L-proteins). The 14-kDa lipoamide-containing H-protein plays a pivotal role in the complete sequence of reactions since its prosthetic group (lipoic acid) interacts successively with the three other components of the complex and undergoes a cycle of reductive methylamination, methylamine transfer and electron transfer. The X-ray crystal structure of different forms of the H-protein has shown a unique conformation of the protein. This leads to the hypothesis of a three-dimensional recognition of the H-protein by the other components of the system and also by the ligase which lipoylates the H-protein. Striking structural similarities are observed between the H-protein and other lipoate domains of 2-oxo acid dehydrogenases and with the biotin carrier protein of acetyl-CoA carboxylase. In the H-protein, the lipoamide arm is free to move in the solvent when oxidized but is pivoted and tightly bound into a cleft at the protein surface when methylamine-loaded. This implies that the H-protein and the T-component form a stable complex during the catalytic transfer of the methylene unit to the tetrahydrofolate cofactor of the T-protein. This complex has been detected by small angle scattering experiments. In conclusion, in the glycine decarboxylase system, the lipoamide arm does not swing freely from one catalytic site to another as was proposed in other systems.
Cohen-Addad
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Institut de Biologie Structurale Jean-Pierre-Ebel, CNRS/CEA, Grenoble, France.
Faure
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Neuburger
M
M
Ober
R
R
Sieker
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L
Bourguignon
J
J
Macherel
D
D
Douce
R
R
D000594:Amino Acid Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D050959:Glycine Decarboxylase Complex; D050961:Glycine Decarboxylase Complex H-Protein; D050841:Glycine Dehydrogenase (Decarboxylating); D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry; D018532:Pisum sativum / Q000201:enzymology*; D018515:Plant Leaves / Q000201:enzymology; D011487:Protein Conformation
D050961:Glycine Decarboxylase Complex H-Protein; D009097:Multienzyme Complexes; D000594:Amino Acid Oxidoreductases; D050959:Glycine Decarboxylase Complex; D050841:Glycine Dehydrogenase (Decarboxylating)